ABSTRACT
Objective To investigate the impact of ultrasound-targeted microbubble destruction ( UTMD) combined with carboplatin sustained release microspheres on the temperature of the tumor microenvironment and the concentration of the drug release in target tumor . Methods Twenty tumor bearing rabbits were randomly assigned into 4 groups : the control group without any treatment ; the carboplatin-loaded PLGA microspheres (CPMs) group ,only intratumoral injection of carboplatin sustained-release microspheres ;the S2000 group ,diagnostic ultrasound irradiation using S2000 equipment on local chemotherapy tumor tissue combined with lipid microbubbles ;the AP-170 group ,the same treatment as the S2000 group except the application of AP-170 instead of S2000 . Far-infrared thermography was performed to measure the tumor temperature . The experimental equipment of extracorporeal circulation was set up . The experimental conditions were assigned into 4 groups :37℃ CPMs group ,37℃ S2000 group ,37℃ AP-170 group ,40℃ AP-170 group . After irradiation experiment ,the carboplatin absorbance was measured at 229 nm wavelength . The absorbance difference of each group was compared with the 37℃ CPMs group ,and each group was tested 10 times . Results The intratumorous temperature in AP-170 group increased to (40 .24 ± 0 .72) ℃ ,which was significantly different from all the other groups ( P ＜ 0 .01).The in vitro drug release experiment showed that the absorbance in the 40 ℃ AP-170 group was 0 .1537 ± 0 .0094 ,which was significantly different from other groups ( P ＜ 0 .01).Higher temperature promoted the release of chemotherapeutic drugs from carboplatin sustained-release microspheres , thus enhanced the chemotherapeutic effect .This might be the mechanism that UTMD affects the microenvironment in this experiment .Conclusions UTMD increases the permeability of tumor cells .The increase of temperature promotes more drugs into the microenvironment of tumor cells .Thus ,the local chemotherapeutic effect is enhanced in the tumor .
ABSTRACT
In this study, we administered a modified schedule of weekly intravenous Bortezomib at 1.6 mg/m(2) with dexamethasone (BD) and compared it to the standard 1.3 mg/m(2) twice-weekly BD regimen in Chinese patients with newly diagnosed multiple myeloma (MM). We assessed the difference in efficacy, safety profile and survival between the once-weekly and twice-weekly cohorts (13 vs. 24 patients). The over response rate was similar with both arms of the study, being 77% in the once-weekly schedule and 74.9% in the twice-weekly schedule (P=0.690). The median overall survival was not reached in either schedule. Also, the median progression-free survival and duration of response of the once-weekly schedule did not significantly differ from those of the twice-weekly schedule (8 months vs.10 months, P=0.545 and 6 months vs.7 months, P=0.467 respectively). Peripheral sensory neuropathy and grade 3/4 hematologic toxic effects were more frequently reported in the twice-weekly schedule than the once-weekly schedule, but there was no statistically significant difference. This preliminary experience in Chinese patients with newly diagnosed MM indicated that once-weekly infusion of Bortezomib plus dexamethasone may improve safety without affecting outcome.
Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Boronic Acids , Bortezomib , Dexamethasone , Multiple Myeloma , Drug Therapy , PyrazinesABSTRACT
In this study, we administered a modified schedule of weekly intravenous Bortezomib at 1.6 mg/m(2) with dexamethasone (BD) and compared it to the standard 1.3 mg/m(2) twice-weekly BD regimen in Chinese patients with newly diagnosed multiple myeloma (MM). We assessed the difference in efficacy, safety profile and survival between the once-weekly and twice-weekly cohorts (13 vs. 24 patients). The over response rate was similar with both arms of the study, being 77% in the once-weekly schedule and 74.9% in the twice-weekly schedule (P=0.690). The median overall survival was not reached in either schedule. Also, the median progression-free survival and duration of response of the once-weekly schedule did not significantly differ from those of the twice-weekly schedule (8 months vs.10 months, P=0.545 and 6 months vs.7 months, P=0.467 respectively). Peripheral sensory neuropathy and grade 3/4 hematologic toxic effects were more frequently reported in the twice-weekly schedule than the once-weekly schedule, but there was no statistically significant difference. This preliminary experience in Chinese patients with newly diagnosed MM indicated that once-weekly infusion of Bortezomib plus dexamethasone may improve safety without affecting outcome.